Reactivity of Rings

Methobromides (54JA2431) and methoiodides [60AP74 63AP38 70-LA(737)24] of perhydropyrido[l,2-c][l,3]oxazines were prepared from the bases with the respective methyl halides. The rates of quaternization of 4-methylperhydropyrido[l,2-o][l,3]oxazmes (70T1217), three isomers of per-hydropyrido[l,2-c][l,3]benzoxazines (21-23) (70T1217), and all isomeric perhydropyrido[3,2,l-y][3,l]benzoxazines (25-28) [80JCS(P2)1778] with methyl iodide were measured in acetonitrile at 29-30°C. 

Copper-mediated 1,4-addition of Grignard reagent (83) to hexahydro-pyrido[l,2-c][l,3]oxazine-l,6-dione (82) afforded perhydro derivatives (84) (93JA8851). Reaction of 1,6-dione (84) with LDA and A-(5-chloro-2-pyridyl)triflimide gave vinyltriflate (81), which contained 10% of the regio-isomeric l,3,4,4a,7,8-hexahydro derivative (93JA8851). 

From the dimethyl acetal derivatives of perhydropyrido[l,2-c][l,3]oxa-zines (33 and 34), the phenylsulfonyl group was reductively removed with sodium amalgam to yield 5-unsubstituted derivatives (96SL100). 

3]oxazine-8-carboxylate with NaOMe in CH3OD gave the 8-deuterated product (81JA7573). 

The anodic electrochemical oxidation of cis-3,4a-H-3-phenylperhydro-pyrido[l,2-c][l,3]oxazin-l-one (91) in methanol in the presence of tetraeth-ylammonium p-toluenesulfonate gave a mixture of methoxylated pyr-ido[l,2-c][l,3]oxazin-l-ones (92-94) (91CJC211). 

The treatment of methyl l-oxo-l,3,4,4u,7,8-hexahydropyrido[l,2-c][l, 3]oxazine-8-carboxylate with NaOMe in CH3OD gave the 8-deuterated product (81JA7573). 

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III. Monocyclic Azines. Relative Reactivity of Rings and Ring-Positions 262... 

Relative reactivity of ring-positions based on positional selectivity of polychloro-azines must be regarded with caution because of the unequal activating effects of the chlorine substituents on each other. Also, it should be emphasized that one cannot use the positional selectivity in di- and tri-substitutions to assess relative reactivity of different positions. In such substitutions, the reactivity is determined by a complex combination of activating and deactivating effects which are unequal at the ring-positions (cf. Sections II, E, 1, II, E, 2,c, and II,E,2,e). 

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